The primary goal of neurological rehabilitation is to restore important motor and cognitive skills that have been impaired by injury or disease. Current therapeutic methods consist primarily of the repeated practice of these skills (e.g., treadmill locomotion, reach and grasp actions) (Wernig and Muller, 1992; Edgerton et al., 1997; Harkema et al., 1997; Taub et al., 1999; Wernig et al., 2000; Edgerton et al., 2001; Maegele et al., 2002; Taub and Uswatte, 2003; Wolf et al., 2006; Edgerton et al., 2008), with the expectation that this practice will lead to plasticity that improves function (Koski et al., 2004; Thickbroom et al., 2004; Thomas and Gorassini, 2005; Yen et al., 2008). Although this strategy is logical and often beneficial, it is seldom completely successful.
The skills that rehabilitation attempts to restore normally depend on plasticity throughout the central nervous system (CNS), from the cerebral cortex to the spinal cord (Drew et al., 2002; Nielsen, 2002; Hultborn and Nielsen, 2007; Wolpaw, 2010; Rossignol and Frigon, 2011). Moreover, the location and nature of the damage that impairs performance differ widely from individual to individual, as well as from disorder to disorder. As a result, the plastic changes (i.e., persistent changes) needed to restore a particular skill (e.g., locomotion) are also likely to differ widely across individuals. Thus, new therapeutic methods that can induce plasticity in particular CNS pathways, and can thereby target each individual's particular deficits, might significantly increase the effectiveness of rehabilitation.
In both animals and humans, operant conditioning protocols can modify specific spinal reflex pathways (Wolpaw and O'Keefe, 1984; Wolpaw, 1987; Chen and Wolpaw, 1995; Wolf and Segal, 1996; Carp et al., 2006a; Chen et al., 2006a; Thompson et al., 2009). Because these spinal pathways participate in important skills such as locomotion, conditioning protocols might be used to reduce the functional deficits produced by spinal cord injuries, strokes, and other disorders. An initial animal study supports this hypothesis. In rats in which a lateralized spinal cord injury (SCI) had produced a gait asymmetry, appropriate conditioning of the soleus H-reflex on the injured side eliminated the asymmetry and restored more normal locomotion (Chen et al., 2006b).
The spinal stretch reflex (SSR) (i.e., the tendon jerk) and its electrical analog, the H-reflex are the simplest motor behaviors. They are produced primarily by a two-neuron, monosynaptic pathway comprised of the primary afferent fiber, its synapse on the motoneuron, and the motoneuron itself (Wolpaw et al., 1983, Wolpaw, 1987). Because it is affected by descending activity from the brain, this pathway can be operantly conditioned. In response to a conditioning protocol, monkeys, humans, rats, and mice can gradually increase (i.e., up-conditioning) or decrease (i.e., down-conditioning) the SSR or the H-reflex (Wolpaw 2010 for review). The larger or smaller reflex that results is a simple motor skill (i.e., “an adaptive behavior acquired through practice” (Chen et al. 2005)). H-reflex conditioning is accompanied by neuronal and synaptic plasticity at multiple sites in the spinal cord and brain (Wolpaw and Chen 2009 for review).
H-reflex conditioning is a powerful model for exploring the mechanisms and principles of skill acquisition and maintenance (Wolpaw 2010). The spinal cord is the final common pathway for all motor behavior, and spinal cord plasticity has a part in the acquisition and maintenance of many motor skills. Furthermore, by virtue of their simplicity, accessibility, separation from the brain, and closeness to behavior, the spinal cord in general and the H-reflex in particular are uniquely suited for studying how activity-dependent plasticity (particularly gradual plasticity) explains behavior, and for formulating concepts and identifying principles that may apply to learning throughout the CNS.
Because the spinal cord is the final common pathway for motor output, the spinal cord plasticity associated with H-reflex conditioning affects other behaviors. For example, in normal rats, right soleus muscle H-reflex up- and down-conditioning produce corresponding changes in the right soleus burst during locomotion (Chen et al. 2005). Nevertheless, despite this change, the right/left symmetry of the step cycle is preserved. This suggests that changes in other reflex pathways compensate for the locomotor effects of the change in the soleus H-reflex pathway. This hypothesis is supported by other evidence that the functional effects of H-reflex conditioning extend beyond the conditioned reflex, and even to the contralateral side of the spinal cord (Wolpaw and Lee 1989).
To date, there is generally a lack of methods, devices, and systems that can be used by subjects and patients to restore and/or improve nervous system functions, particularly in a self-administered or outpatient manner. Therefore, novel strategies that can complement current methods and thereby enhance and/or restore important motor and cognitive skills that have been impaired by injury or disease are needed.
The present invention is directed to overcoming the current deficiencies in the art of neurological rehabilitation.